The major objectives of this study are to determine the nature of proteins forming intracellular complexes with potentially toxic metals, particularly lead and mercury. Both of these metals are known to bind intracellularly with acid nuclear proteins. It is not known whether these proteins are synthesized specifically for binding with these metals. Experiments are planned to determine the role of de novo synthesis on the availability of the proteins. Rats exposed to excessive amounts of lead and mercury will be treated with metabolic inhibitors of protein synthesis and acidic nuclear protein-metal complexes will be isolated and compared quantitatively with intoxicated rats not treated with metabolic inhibitors. If it is found that treatment by inhibitors of protein synthesis (e.g., cycloheximide and/or actinomycin D) inhibits lead protein formation, the toxic effects of the same amounts of metal will be compared in treated and untreated rats. If protein-metal complexing is desirable, as suspected from studies to date, possible induction of lead and/or mercury binding acidic nuclear proteins will be studied by prior exposure to less toxic essential metals, zinc and/or copper. These studies should contribute toward understanding (1) variation in susceptibility of different individuals in the population to the toxic effects of metals encountered in industrial exposure or in the ambient environment, and (2) may determine possible ways of inducing protective metal-binding proteins by administration of less toxic metals.